[Evaluation of aerogenic occupational health risk for workers engaged into periclase-carbon refractories production].
The work is aimed to evaluate aerogenic occupational health risk for workers engaged into preparation and formation of technologic mass in periclase-carbon refractories production, using organic binding agent according to criteria R 2.2.2006-05 and R 2.2.1716-03. Occupational dust is a complicated chemical mixture containing manganum oxide, phenol, formaldehyde, aerosols containing silicon, benzpyrene (if "Carbores" binding agent used). Hygienic evaluation revealed occupational health risk due to occupational dust at workplaces of runners operator, press operator, batching feeder, crane operator. Aerogenic occupational risk at workplace of grinder operator is assessed as negligibly small (tolerable). Experimental and epidemiologic studies prove probable (proof category 1B) occupational risk of respiratory disease at the studied production.


Inactivation of norovirus and surrogates by natural phytochemicals and bioactive substances.
Human norovirus is the leading cause of sporadic gastroenteritis, which is responsible for more than 90% of all nonbacterial gastroenteritis outbreaks. While norovirus infections typically cause mild and self-limiting symptoms lasting 24-48 h, chronic persistent infections can cause severe symptoms. Although recent advances have been made in understanding the molecular characteristics of norovirus infection, no norovirus-specific antiviral drugs, or vaccines are available. Conventional intervention methods used to inactivate norovirus, such as treatment with disinfecting agents (e.g. ethanol, hypochlorite, and quaternary ammonium formulations), have shown a lack of efficacy against human norovirus when they are applied to foods and in food preparation processes. Therefore, alternative antiviral or inactivating agents such as phytochemicals have received attention as potential norovirus inhibitors due to their relatively low toxicity and lack of side effects, which allows them to be prepared as food-safe formulations. Evidence from studies using viral surrogates suggests that numerous phytochemicals and foods containing flavonoids and polyphenols have anti-norovirus activity, and future studies will be necessary to confirm the effectiveness of such compounds against human norovirus and the molecular mechanisms through which they produce antiviral effects.


Pyridoxine neuropathy.
A case of sensory neuropathy in a young woman due to long-term ingestion of pyridoxine, with subsequent recovery, is described. Pyridoxine neuropathy may occur after the long-term ingestion of doses as low as 200 mg a day. Because of its widespread use in the community, both the general public and the medical community need to be aware of this recently described complication of megavitamin therapy.


Effects of Glucose Concentration on Propofol Cardioprotection against Myocardial Ischemia Reperfusion Injury in Isolated Rat Hearts.
The anesthetic propofol confers cardioprotection against myocardial ischemia-reperfusion injury (IRI) by reducing reactive oxygen species (ROS). However, its cardioprotection on patients is inconsistent. Similarly, the beneficial effect of tight glycemic control during cardiac surgery in patients has recently been questioned. We postulated that low glucose (LG) may promote ROS formation through enhancing fatty acid (FA) oxidation and unmask propofol cardioprotection during IRI. Rat hearts were isolated and randomly assigned to be perfused with Krebs-Henseleit solution with glucose at 5.5 mM (LG) or 8 mM (G) in the absence or presence of propofol (5 μg/mL) or propofol plus trimetazidine (TMZ). Hearts were subjected to 35 minutes of ischemia followed by 60 minutes of reperfusion. Myocardial infarct size (IS) and cardiac CK-MB were significantly higher in LG than in G group (P < 0.05), associated with reduced left ventricular developed pressure and increases in postischemic cardiac contracture. Cardiac 15-F2t-isoprostane was higher, accompanied with higher cardiac lipid transporter CD36 protein expression in LG. Propofol reduced IS, improved cardiac function, and reduced CD36 in G but not in LG. TMZ facilitated propofol cardioprotection in LG. Therefore, isolated heart with low glucose lost sensitivity to propofol treatment through enhancing FA oxidation and TMZ supplementation restored the sensitivity to propofol.


Gypsy transposition correlates with the production of a retroviral envelope-like protein under the tissue-specific control of the Drosophila flamenco gene.
Gypsy displays striking similarities to vertebrate retroviruses, including the presence of a yet uncharacterized additional open reading frame (ORF3) and the recent evidence for infectivity. It is mobilized with high frequency in the germline of the progeny of females homozygous for the flamenco permissive mutation. We report the characterization of a gypsy subgenomic ORF3 RNA encoding typical retroviral envelope proteins. In females, env expression is strongly repressed by one copy of the non-permissive allele of flamenco. A less dramatic reduction in the accumulation of other transcripts and retrotranscripts is also observed. These effects correlate well with the inhibition of gypsy transposition in the progeny of these females, and are therefore likely to be responsible for this phenomenon. The effects of flamenco on gypsy expression are apparently restricted to the somatic follicle cells that surround the maternal germline. Moreover, permissive follicle cells display a typically polarized distribution of gypsy RNAs and envelope proteins, both being mainly accumulated at the apical pole, close to the oocyte. We propose a model suggesting that gypsy germinal transposition might occur only in individuals that have maternally inherited enveloped gypsy particles due to infection of the maternal germline by the soma.


Risk Factors for Infection After Minor Dermatologic Procedures: A Case-Control Study.
There are limited published data regarding the incidence and risk factors for infection after minor dermatologic procedures, such as skin biopsy, shave, and curettage. Prior studies of infection risk after dermatologic procedures have often not specified the method of preparation of local anesthetic. To assess the incidence and risk factors for infection after minor procedures performed in a general dermatology clinic using buffered lidocaine prepared in office. In this retrospective case-control study, the medical record was searched for cases of infection after skin biopsies, shaves, conventional excisions, and destructions performed in a general dermatology clinic over a 4-year period. Patient and procedure characteristics were compared with uninfected controls. Of 9,031 procedures performed during the study period, there were 34 infections (0.4%). The odds of infection for procedures on the arm and leg were 5.29 and 9.28 times higher, respectively, than those on the head/neck. There was no significant effect of age, sex, smoking, immunosuppression, diabetes, or anticoagulation. The incidence of infection is low after minor dermatologic procedures performed with local anesthesia using buffered lidocaine prepared in office. There is a higher risk of infection on the arm and leg compared with the head and neck.


Hemoglobin-mediated lipid oxidation and compositional characteristics of washed fish mince model systems made from cod (Gadus morhua), herring (Clupea harengus), and salmon (Salmo salar) muscle.
The use of washed cod light muscle minces in mechanistic studies of hemoglobin (Hb)-mediated fish lipid oxidation has largely increased in the past 5 years. Although cod light muscle has a low level of intrinsic lipid oxidation catalysts, a prerequisite for a good oxidation model system, we believe it cannot fully mimic the oxidation kinetics taking place in other fish species being more susceptible to lipid oxidation. The aim of this study was to systematically investigate whether washed mince model systems useful in Hb-mediated oxidation studies could be prepared also from herring (Clupea harengus) and salmon (Salmo salar) light muscles. The kinetics of oxidation in the washed models was measured during ice storage (+/-Hb), and the results were related to compositional differences. Minces from cod, herring, and salmon light muscles were washed 3 times with 3 volumes of water and buffer. A 20 microM portion of Hb and 200 ppm streptomycin was then added, followed by adjustment of pH and moisture to 6.3 and 86%, respectively. Samples with or without Hb were then stored on ice, and oxidation was followed as peroxide value (PV), rancid odor, redness (a*) loss and yellowness (b*). Prior to storage, all minces and models were also analyzed for total lipids, fatty acids, alpha-tocopherol, proteins, Hb, Fe, Cu, and Zn. Hb-mediated lipid oxidation appeared within 2 days on ice in all models. Small differences in the oxidation rates ranked the models as herring > cod > salmon. These differences were ascribed to more preformed peroxides and trace elements in the herring model, and more antioxidants in the salmon model. Controls, without Hb, stayed stable in all cases except herring, where a very slight oxidation appeared, especially if the herring raw material had been prefrozen. In conclusion, fattier fish like dark muscle species and salmonoids are useful for making washed mince model systems and would be a better choice than cod if there is an interest in the oxidation kinetics of such species.


Chironomidae (Midge) Sensitivities to Ammonia Using Multiple Endpoints in China and Australia for the Development of Water Quality Criteria for Freshwater River Systems in China.
Deriving water quality criteria (WQC) for aquatic risk assessment requires sufficient toxicity data, which can determine the accuracy of WQC. Given that toxicity data vary between test species and endpoints, there is a great need to compare such data to generate the most suitable data set for WQC derivation. In the present study, a series of 11 ammonia exposure bioassays were conducted on Chironomidae species in either China or Australia, with test species and test endpoints varied (2 Chironomus sp., enzymatic up to lethal endpoints, and no-observed-effect concentration up to median lethal concentration [LC50] as endpoint metrics). There were no statistically significant differences between toxicity results generated from China compared to Australia using Chironomus sp., indicating that published data on native species generated in different countries could be appropriate for inclusion in the development of local Chinese WQC. In addition, the Chironomidae larvae laboratory-based toxicity value (LC50 = 384.6 mg/L) was lower than that of the in situ field-based toxicity value (LC50 ≥ 451.2 mg/L) where sensitive life stages are used, and, specifically for C. riparius, endpoints linked to biochemical and gene expression effects could be as sensitive as or more sensitive than chronic endpoints, both of which were more sensitive than acute endpoints. These findings help in the development of WQC by demonstrating the suitability of inclusion of toxicity data from a range of sources, as well as adding to the overall pool of knowledge regarding sensitivity to ammonia which can be used in aquatic risk assessment. Environ Toxicol Chem 2021;40:2899-2911. © 2021 SETAC.


Lapatinib side-effect management.
Lapatinib is an oral dual tyrosine kinase inhibitor targeting epidermal growth factor receptor and HER2. Diarrhea and dermatologic adverse events are reported commonly by patients treated with lapatinib. Diarrhea can range from mild to severe based on the agents used in combination with lapatinib. The adverse events may diminish quality of life, reduce treatment adherence, and lead to discontinuation of therapy. Consequently, proactive management of diarrhea is crucial, especially in patients receiving lapatinib in combination with other agents that also cause diarrhea. As the utility of lapatinib expands, crucial proactive diarrhea-management and dose-reduction strategies are evolving to decrease the likelihood of grade 3 or 4 toxicity. With regard to dermatologic adverse events, most are mild to moderate in severity, are of limited duration, and frequently do not require treatment intervention. However, in some patients, management of dermatologic adverse events is of great importance. This article reviews data regarding diarrhea and dermatologic adverse events in patients treated with lapatinib and summarizes the key role that oncology nurses play in educating patients about the potential for adverse events and the importance of preventive measures, ongoing surveillance, appropriate treatment, and dose reductions.


Genetic modelling of the estrogen metabolism as a risk factor of hormone-dependent disorders.
Estradiol is a pleiotropic hormone, involved in the etiology of a wide variety of diseases. Over the last decade individual genetic variability of the estradiol metabolism has been described as a significant contributor to disease susceptibility with variations depending on ethnic background. Among others, genetic variations of genes encoding cytochrome P450 (CYP) enzymes play an important role in this regard. Mutant alleles of the CYP 1A1 gene are major modulators of lung cancer risk among smokers, mediate gender differences in lung cancer susceptibility, and have been associated with an elevated risk for developing breast, prostate, colorectal, and oral squamous cell cancer. Variants of the CYP 1B1 gene modulate the risk for developing prostate, ovarian, lung, and breast cancer. Also, mutations in the CYP 1B1 gene are the major genetic determinant of congenital glaucoma. Mutant CYP 17 alleles are associated with serum and plasma levels of steroid hormones, use of hormone replacement therapy, and the development of endometrial, prostate, and breast cancer. Available data indicate that the protective effect against breast cancer of a later age at menarche is limited to wild-type CYP 17 allele carriers. Among women with the polycystic ovary syndrome, carriage of mutant CYP 17 alleles is sufficient to aggravate the clinical presentation of the disease. Molecular variants of the CYP 19 gene are associated with an increased risk for developing breast cancer, advanced breast cancer stages, and tumor aromatase production. Carriage of a mutant catechol-O-methyltransferase allele is associated with breast cancer, neurologic disorders such as Parkinson's disease, and modulates behavior among patients with schizophrenia, alcoholics and the general population. In summary, the available evidence points to genes that encode estrogen-metabolizing enzymes as strong hereditary determinants of the susceptibility to benign as well as malignant conditions.


The roles of the anterior tonsillar pillar and previous tonsillectomy on sleep-disordered breathing.
We conducted a study to determine if there is a correlation between inadequate anterior tonsillar pillar support and sleep-disordered breathing. We examined 11 patients with a history of tonsillectomy to ascertain the structural and functional integrity of their anterior tonsillar pillars. All 11 demonstrated a loss of anterior pillar support and collapse of their soft palate to the extent that the soft palate passively pressed against the posterior pharyngeal wall. We conclude that a deficiency of anterior tonsillar pillar support does indeed predispose patients to obstructive sleep apnea syndrome. Knowledge of this correlation can help guide the method of surgical treatment and should reinforce the need to maintain the integrity of the anterior tonsillar pillars.


Effects of the characteristic temperament of cats on the emotions and hemodynamic responses of humans.
Cats positive effects on their owners' physiological and psychological health, including improved mood and activation of the human prefrontal cortex and inferior frontal gyrus in the brain. However, the association between the health benefits provided by cat ownership and the characteristic behaviors and reactions of cats is unclear. We recruited 29 participants to measure human prefrontal cortex activity, using functional near-infrared spectroscopy, during interactions with a cat. After the experiments, participants subjectively responded to a questionnaire regarding success rates for interactions with the cat, and completed the Self-assessment Manikin-a scale used to measure emotion. Interactions comprised eight types in four categories (touch, play, train, and feed). This study showed that interactions with a cat significantly activated the prefrontal cortex, regardless of interaction type. During training, the integral values of oxygenated hemoglobin in the left inferior frontal gyrus were the highest in all the interaction categories; however, success rates were lower than in the touch and feed interactions. Regarding the Self-assessment Manikin scores, all interaction categories showed a positive correlation between success rate and valence score, especially in the train and play interactions than in the touch and feed interactions. These results indicate that interactions with a cat activate the prefrontal cortex in humans, including the inferior frontal gyrus region. Moreover, cats' autonomous behaviors and reactions positively influenced the participants. The characteristic temperament of cats may be a key factor influencing the health benefits of owning cats.


Protocol for process evaluation of evidence-based care pathways: the case of colorectal cancer surgery.
Care pathways are complex interventions, consisting of multiple 'active ingredients', to structure care processes around patient needs. Numerous studies have reported improved outcomes after implementation of care pathways. The structure-process-outcome framework and the context-mechanism-outcome framework both suggest that outcomes can only be achieved through a certain process within a context or structure. To understand how and why care pathways are effective, understanding of both this process and context is necessary. The aim of this article is to propose a study protocol to evaluate the implementation process of evidence-based care pathways, including the influence of the context. This protocol is explained by applying it to the implementation of a colorectal cancer surgery pathway in an international setting. The Medical Research Council (MRC) guidance on process evaluations for complex interventions is used as the basis for the protocol. The key components of process evaluation are intervention, context, implementation, mechanisms of impact and outcomes. In process evaluations, these components are studied using quantitative and qualitative methods. Among them are patient record analysis, questionnaires, on-site visits and interviews. To guide our methodological choices, the MRC guidance for process evaluations of complex interventions, and published protocols for process evaluations of complex interventions were used. Our protocol is now tailored for the process evaluation of evidence-based care pathways and provides researchers and clinicians methods and tools, as well as a worked example, that can be used to study the process of care pathway implementation. As a result, healthcare professionals will be informed on context factors and implementation processes that can facilitate the implementation of care pathways, improving quality and effectiveness of care processes.


[Effect of mitochondrial dysfunction in diabetic cardiomyopathy and intervention of traditional Chinese medicine].
Diabetic cardiomyopathy (DCM) is characterized by left ventricular hypertrophy, myocardial fibrosis and diastolic dysfunction, which are uncorrelated with underlying coronary artery disease or hypertension. As an important metabolic organelle, mitochondria directly involve the process of cell growth, proliferation, signal transduction, apoptosis and so on. Recent studies have demonstrated a close correlation between the mitochondrial dysfunction and the pathogenesis of diabetic cardiomyopathy. The underlying effects of mitochondrial dysfunction in the progress of diabetic cardiomyopathy involve disturbed metabolism, oxidative stress, defective calcium handling, mitochondrial uncoupling, apoptosis, imbalance of mitochondrial quality control and regulation of MicroRNAs. Traditional Chinese medicines have been widely applied in clinic. Nowadays, more and more herbs of extracts of traditional Chinese medicines have been proved to ameliorate diabetic myocardial injury. Because the improvement of mitochondrial dysfunction has emerged as a promising therapeutic strategy, this review summarizes these effects of mitochondrial dysfunction in diabetic cardiomyopathy, and discusses the intervention studies of traditional Chinese medicine in the field, in expectation to provide new ideas for DCM prevention and treatment.


The addition of a large caliber needle during endoscopic ultrasound-guided fine needle aspiration of solid and lymph node lesions: any importance?
The benefits of using multiple gauge needles during EUS-FNA of solid and lymph node lesions are unknown. The purpose of our study was to find out the significance of adding a large caliber needle if small caliber needle fail to achieve diagnostic specimen after few passes. It was a retrospective review of all EUS-FNA procedures performed by one of the two experienced endosonographers. A large (22 or 19 gauge) needle was added if on-site cytologic analysis did not reveal adequate specimen after ≥2 passes. The adequacy of the specimen was determined by the Cytopathologist, and categorized as either satisfactory for analysis or unsatisfactory. The cytologic findings were reported as either benign or malignant. Out of total 1200 EUS cases, FNA was performed in 306 cases with different solid and lymph node lesions. Multiple gauge needles were used in 188/306 (39%) cases. There was no statistically significant difference in the diagnostic yield and definitive diagnosis between multiple and single gauge needle groups. The finding was unchanged after controlling the number of needle passes. No complications were noted. The addition of a large caliber needle achieved at least the same (or even slightly higher diagnostic yield), and can be a method of rescue in certain cases.


Seroepidemiology of Q fever in New Brunswick and Manitoba.
A seroepidemiological survey, using an indirect immunofluorescence test, was carried out on serum samples obtained from New Brunswick and Manitoba blood donors during 1986. The antigens were Coxiella burnetii phase I and phase II from strain Nine Mile. Eighty of the 503 (15.9%) Manitoba blood donors had a phase II antibody titer of greater than or equal to 1:8, while 41 (4.2%) of the 966 New Brunswick blood donors had such antibodies. We have recently diagnosed three cases of Q fever in New Brunswick but none have been diagnosed in Manitoba. Our data suggest that Q fever may be increasing in New Brunswick and repeated seroepidemiological studies are indicated. It is likely that undetected cases of Q fever are occurring in Manitoba.


Is Complex Visual Information Implicated During Language Comprehension? The Case of Cast Shadows.
Previous research showed that sensorimotor information affects the perception of properties associated with implied perceptual context during language comprehension. Three experiments addressed a novel question of whether perceptual context may contribute to a simulation of information about such out-of-sight objects as cast shadows. In Experiment 1, participants read a sentence that implied a particular shadow cast on a target (blinds vs. an open window) and then verified the picture of the object onto which a shadow was cast. Responses were faster when the shadow of blinds cast on the object matched that implied by the sentence. However, the data did not show the same matching effect for pictures with cast shadows from an open window. In Experiments 2 and 3, we found that verification times for pictures with no cast shadows were faster when preceded by an "open window" sentence, thus suggesting that reading the sentence does not elicit a visual simulation of any specific shadow. Experiment 3 showed that the objects superimposed with a cast shadow of the blinds and blinds themselves were verified faster after reading a "blinds" sentence. However, the results of an order analysis showed the temporal stability of the "blinds shadows" effect, but the disappearance of the "blinds" effect in the second half of the data. We conclude that the results are compatible, to a lesser or greater extent, with multiple accounts, and discuss our findings in the context of a mental imagery view, a mental simulation view, and an amodal representation view.


Managing female pelvic floor disorders: a medical device review and appraisal.
Pelvic floor disorders (PFDs) will affect most women during their lifetime. Sequelae such as pelvic organ prolapse, stress urinary incontinence, chronic pain and dyspareunia significantly impact overall quality of life. Interventions to manage or eliminate symptoms from PFDs aim to restore support of the pelvic floor. Pessaries have been used to mechanically counteract PFDs for thousands of years, but do not offer a cure. By contrast, surgically implanted grafts or mesh offer patients a more permanent resolution but have been in wide use within the pelvis for less than 30 years. In this perspective review, we provide an overview of the main theories underpinning PFD pathogenesis and the animal models used to investigate it. We highlight the clinical outcomes of mesh and grafts before exploring studies performed to elucidate tissue level effects and bioengineering considerations. Considering recent turmoil surrounding transvaginal mesh, the role of pessaries, an impermanent method, is examined as a means to address patients with PFDs.


Integrated predictive model for prostatic cancer using clinical, laboratory and ultrasound data.
to develop a predictive model to estimate the probability of prostate cancer prior to biopsy. from September 2009 to January 2014, 445 men underwent prostate biopsy in a radiology service. We excluded from the study patients with diseases that could compromise the data analysis, who had undergone prostatic resection or used 5-alpha-reductase inhibitors. Thus, we selected 412 patients. Variables included in the model were age, prostate specific antigen (PSA), digital rectal examination, prostate volume and abnormal sonographic findings. We constructed Receiver Operating Characteristic (ROC) curves and calculated the areas under the curve, as well as the model's Positive Predictive Value (PPV) . of the 412 men, 155 (37.62%) had prostate cancer (PC). The mean age was 63.8 years and the median PSA was 7.22ng/ml. In addition, 21.6% and 20.6% of patients had abnormalities on digital rectal examination and image suggestive of cancer by ultrasound, respectively. The median prostate volume and PSA density were 45.15cm3 and 0.15ng/ml/cm3, respectively. Univariate and multivariate analyses showed that only five studied risk factors are predictors of PC in the study (p<0.05). The PSA density was excluded from the model (p=0.314). The area under the ROC curve for PC prediction was 0.86. The PPV was 48.08% for 95%sensitivity and 52.37% for 90% sensitivity. the results indicate that clinical, laboratory and ultrasound data, besides easily obtained, can better stratify the risk of patients undergoing prostate biopsy.


Dynamics of distorted cholesterics in a mesogenic versus isotropic polymer network.
The dynamics of the distorted cholesteric director is studied in a complex matrix, such as mesogenic and istotropic polymer networks, by means of dynamic light scattering. We employ polymer-stabilized cholesteric diffraction gratings as our system to measure thermal fluctuations of the cholesteric director in photostabilized low-molecular-weight polymer networks. The relaxation rates of fast and slow dynamical modes of the distorted cholesteric directors are measured in two scattering geometries, where the scattering vector is either parallel or perpendicular to the helical axis. The dispersion relations for fluctuation wave vectors along the helical axis are found to be fundamentally different for the two types of polymer networks. Experimental dispersion curves are in agreement with the theoretical predictions developed in the present paper. A possible understanding of dispersion in distorted cholesterics is developed and the experimental results for polymer stabilized cholesteric diffraction gratings are presented in this report. We also discuss the coupling of a slow relaxation mode of distorted cholesterics in a mesogenic versus isotropic polymer network.


[Evaluation of low-dose amphotericin B and flucytosine in the treatment of cryptococcal meningitis].
To evaluate the efficacy and safety of low-dose amphotericin B (< 0.7 mg x kg(-1) x d(-1)) and flucytosine in patients with non-AIDS-associated cryptococcal meningitis. In non-AIDS patients with cryptococcal meningitis admitted to Huashan Hospital, Fudan University in Shanghai from January 1998 to December 2007, 31 were initially treated with low-dose amphotericin B and flucytosine for more than 1 week. The clinical characteristics, clinical responses, drug-related adverse reactions and outcome of these patients were retrospectively evaluated. Among the 31 patients enrolled in this study, 8 patients had one or more predisposing factors. Headache, fever, meningeal irritation and vomiting were common clinical symptoms and signs when cryptococcal meningitis was diagnosed. The result of cranial CT scan and/or MRI showed abnormality in 22 cases (78.6%). When the therapy of low-dose amphotericin B and flucytosine ended, the complete response rate was 19.4% (6/31), partial response rate was 54.8% (17/31), and total effective rate was 74.2%. Except for 1 patient lost to follow-up, the 1-year attributable and all-cause mortality among the remaining 30 patients were 0 (0/30) and 10.0% (3/30) respectively. On the other hand, 26 (83.9%) patients had amphotericin B-related adverse reactions, including renal impairment, liver injury, arrhythmia, and anemia, etc. However, most of these reactions were tolerable. Low-dose amphotericin B and flucytosine can be used in non-AIDS-associated cryptococcal meningitis with both acceptable efficacy and safety.


Genetic Signatures of Asthma Exacerbation.
Asthma exacerbation (AE) usually denotes worsening of asthma symptoms that requires intense management to prevent further deterioration. AE has been reported to correlate with clinical and demographic factors, such as race, gender, and treatment compliance as well as environmental factors, such as viral infection, smoking, and air pollution. In addition, recent observations suggest that there are likely to be genetic factors specific to AE. Understanding genetic factors specific to AE is essential to develop therapy tailored for exacerbation-prone asthma. Here, we summarize the results of studies involving genetic risk factors for AE. To simplify and enhance understanding, we reviewed the studies according to the following categories: hypothesis-driven approaches, hypothesis-free approaches, gene-environment interactions, and pharmacogenetics.


Third Advances Against Aspergillosis Meeting 2008.
On 16-19 January 2008, the Third Advances Against Aspergillosis Meeting took place in Miami Beach, FL, USA. There were 351 registrants from 26 countries. The two earlier meetings had taken place in San Francisco, CA, 2004 and in Athens, Greece, 2006, and the series has become the place for scientists and clinicians to be updated on developments relevant to all aspects of this fungal genus.


Mammalian epidermal messenger RNA: identification and characterization of the keratin messengers.
A messenger RNA fraction which directs the synthesis of epidermal keratins and other skin proteins has been isolated from adult guinea pigs and newborn rats, utilizing techniques designed to minimize degradation by endogenous nucleases. During the initial extraction procedures an inhibitor of translation was identified. This inhibitor could be removed by sedimentation of the RNA through cesium chloride. Electrophoresis of the resulting RNA on denaturing agarose/urea gels indicated that, in addition to 18S and 28S ribosomal RNAs, several minor species ranging in size from 10S to 28S were present. This heterogeneous RNA stimulated the incorporation of radioactive amino acids into protein in a reticulocyte lysate system which had an absolute dependence on added mRNA. A fraction of the RNA was retained on oligo(dT)-cellulose, indicating the presence of poly(adenylic acid) sequences. This poly(A)-rich material was considerably enriched for mRNA activity. Analysis of the products of synthesis indicated that proteins which migrated as keratins in 1- and 2-dimensional electrophoretic systems were major translation products of both the unfractionated material and poly(A)-containing fractions. The minimum sedimentation coefficient of keratin mRNAs was found to be 18S, a value consistent with the molecular weight of the keratin polypeptides.


miR-125a-5p is a prognostic biomarker that targets HDAC4 to suppress breast tumorigenesis.
Identifying stably expressed tumor markers that can be used easily to detect cancer is currently an important area of cancer research. By using miRNA microarray, we identified 20 differentially expressed miRNAs in serum samples of breast cancer patients. Expression of miR-125a-5p was relatively lower in patients with shorter survival compared to long-term survivors. In a cohort of breast cancer patients (N = 300), serum expression of miR-125a-5p was negatively and significantly correlated with tumor grade (P = 0.004), lymph-node status (P = 0.004), and tumor size (P < 0.001). Low miR-125a-5p expression was an independent prognostic marker (OR = 0.421; 95% CI = 0.184 to 0.961; P = 0.04) associated with poor survival rates (P = 0.0062). We show that miR-125a-5p directly inhibits expression of the HDAC4 gene, resulting in tumor suppression in vitro and in vivo. Together these results demonstrate that serum miR-125a-5p level in breast cancer may be a useful prognostic biomarker and offer a novel therapeutic avenue by targeting HDAC4 in breast cancer.


Being on top.
Academics are fascinated by sex workers and until recently the subjects of this research gaze have been kept in a subordinate position. This contribution considers the different kinds of knowledge production that pertain to the field of sex work research and analyses the politics and tensions involved in these layers of knowledge production. The contribution does not intend to show that some forms of research are 'better' than others in regard to sex workers' rights, though some forms undoubtably are more effective. Rather it draws on frameworks that sex workers have developed to critique injustice, specifically whorephobia, to reveal the unwavering structure of oppression written into academia and research. The contribution upends existing ways of seeing these concerns by placing whores in a position to save researchers from academic disciplining by explicating struggles over resources (funding, employment, social capital and authority) so that our collective contributions to the production of knowledge are sincere and revolutionary. The author concludes that sex workers' desire for change is not unruliness to be contained, controlled, dismissed and/or destroyed; it is an advantage in the creation of knowledge and the path to radical, needed transformations in the extractive logics that pervade academia.


Learning New Vocabulary Implicitly During Sleep Transfers With Cross-Modal Generalization Into Wakefulness.
New information can be learned during sleep but the extent to which we can access this knowledge after awakening is far less understood. Using a novel Associative Transfer Learning paradigm, we show that, after hearing unknown Japanese words with sounds referring to their meaning during sleep, participants could identify the images depicting the meaning of newly acquired Japanese words after awakening (N = 22). Moreover, we demonstrate that this cross-modal generalization is implicit, meaning that participants remain unaware of this knowledge. Using electroencephalography, we further show that frontal slow-wave responses to auditory stimuli during sleep predicted memory performance after awakening. This neural signature of memory formation gradually emerged over the course of the sleep phase, highlighting the dynamics of associative learning during sleep. This study provides novel evidence that the formation of new associative memories can be traced back to the dynamics of slow-wave responses to stimuli during sleep and that their implicit transfer into wakefulness can be generalized across sensory modalities.


Combination drug chemotherapy and massive skeletal allograft in the management of hydatid disease of femur.
Hydatid disease of long bone is a rare presentation. Chemotherapy and surgery constitute the standard treatment of choice. Non-union of a pathological fracture of femur particularly due to hydatid disease has been known to be resistant to treatment. These resistant cases require combination drug chemotherapy and excision of the lesion. Reconstruction of a large skeletal defect following resection of the lesion poses a challenge to the orthopaedic surgeons. We discuss the staged treatment of hydatid disease of shaft of femur with resection and cement spacer application followed by reconstruction using massive skeletal allograft under cover of combination drug chemotherapy.


[An approach to evaluation methods for laboratory work].
Evaluation methods were proposed for quality control, normal range calculation and laboratory diagnosis. As a quality control method, the Xbar-R control chart should be evaluated with an error detection chart or with operating characteristic functions. Normal range calculation was evaluated by three parameters, accuracy, precision and robustness which represents stability against abnormal data contamination. Prior to evaluating the laboratory diagnosis, patient data were plotted on a three dimensional chart, a star map, to determine whether apparent clusters were formed. Laboratory diagnosis is a process of reduction of multivariate medical information, and it develops new parameters related to the pathological state of the patient. The method was evaluated using entropy calculation or average count of abnormal parameters.


Invasive pneumococcal disease in relation to vaccine type serotypes.
Since 1983 the world has been introduced to four vaccines combating disease caused by Streptococcus pneumoniae bacteria. However, despite vaccination programs disease caused by S. pneumoniae continues to lead to high morbidity and mortality worldwide. Surprisingly, instances of invasive pneumococcal disease (IPD) are still highly attributed to serotypes found in the current vaccine, such as serotypes 3 and 19A. Conversely, non-conjugate vaccine serotypes, such as 35B, are increasing and of rising interest. The persistence of vaccine type serotypes and the increase in non-conjugate vaccine type serotypes show the need for further research into conjugate vaccine design and the need for novel strategies to combat IPD. Abbreviation: IPD: invasive pneumococcal disease.


Biofilm-Templated Heteroatom-Doped Carbon-Palladium Nanocomposite Catalyst for Hexavalent Chromium Reduction.
In this study, we report an interdisciplinary and novel strategy toward biofilm engineering for the development of a biofilm-templated heteroatom-doped catalytic system through bioreduction and biofilm matrix-facilitated immobilization of the in situ-formed catalytic nanoparticles followed by controlled pyrolysis. We showed that (i) even under room temperature and bulk aerobic conditions, Shewanella oneidensis MR-1 biofilms reduced Pd(II) to form Pd(0) nanocrystals (∼10 to 20 nm) that were immobilized in the biofilm matrix and in cellular membranes, (ii) the MR-1 biofilms with the immobilized Pd(0) nanocrystals exhibited nanocatalytic activity, (iii) exposure to Pd(II) greatly increased the rate of cell detachment from the biofilm and posed a risk of biofilm dispersal, (iv) controlled pyrolysis (carbonization) of the biofilm led to the formation of a stable heteroatom-doped carbon-palladium (C-Pd) nanocomposite catalyst, and (v) the biofilm-templated C-Pd nanocomposite catalyst exhibited a high Cr(VI) reduction activity and maintained a high reduction rate over multiple catalytic cycles. Considering that bacteria are capable of synthesizing a wide range of metal and metalloid nanoparticles, the biofilm-templated approach for the fabrication of the catalytic C-Pd nanocomposite we have demonstrated here should prove to be widely applicable for the production of different nanocomposites that are of importance to various environmental applications.


Retinal degeneration in rats induced by CI-1010, a 2-nitroimidazole radiosensitizer.
The anti-cancer compound CI-1010, designated as (R)-alpha-([(2-bromoethyl)amino]methyl)-2-nitro-1H-imidazole-1-ethanol monohydrobromide, has a proposed dual mechanism of action due to alkylating and radiosensitizing activities. To assess potential toxicity, adult Wistar rats were treated with a single intravenous injection (0, 50, 100, 150, 225, or 350 mg/kg) and necropsied at 4 or 29 days following treatment. In a repeated dose experiment, rats were injected daily (0, 10, 40, or 80 mg/kg; 5 doses/wk) for 3 wk and necropsied at the end of week 3 or 7. CI-1010 induced retinal degeneration by 4 days after a single injection of > or = 225 mg/kg or by 3 wk of repeated injections of > or = 40 mg/kg. The locally extensive to diffuse retinal degeneration involved the photoreceptor and outer nuclear layer. The photoreceptor layer was vacuolated and compressed corresponding to ultrastructural evidence of inner segment swelling and outer segment fragmentation. The outer nuclear layer was thinned due to loss of nuclei and contained numerous pyknotic or karyorrhectic nuclei. These nuclear changes were morphologically consistent with apoptosis and many outer nuclear layer nuclei labeled with in situ TdT-mediated dUTP-digoxigenin nick end labeling (Apoptag). The retinal degeneration was nonreversible, evidenced by increased lesion severity and incidence after CI-1010 was withdrawn for either 25 or 28 days.


Heat shock-induced HIKESHI protects cell viability via nuclear translocation of heat shock protein 70.
Heat shock proteins (HSPs), particularly HSP70, help restore normal cellular function following damage caused by stressors. HSP expression in tumor tissues indicates cancer progression, and while the development of HSP inhibitors is progressing, these substances are not widely used to treat cancer. HIKESHI (C11orf73) does not control the intracellular movement of HSP70 at normal temperatures; however, it does regulate the function and movements of HSP70 during heat shock. In this study, we examined the intracellular movement of HSP70 during heat shock to investigate the significance of HIKESHI expression in gastric cancer (GC) and determine if HIKESHI inhibition has cytotoxic effects. We examined HIKESHI using GC cell lines and immunostaining in 207 GC tissue samples. HIKESHI expression in GC tissues was associated with the progression of lymphatic invasion. Suppressing HIKESHI using siRNA did not affect cell viability at normal temperatures. However, suppressing HIKESHI during heat shock inhibited HSP70 nuclear transport and suppressed cell viability. Our results suggest that HIKESHI is a marker of cancer progression and that the combination of HIKESHI inhibition and hyperthermia is a therapeutic tool for refractory GC.


A prospective study of dietary carbohydrate quantity and quality in relation to risk of ovulatory infertility.
To evaluate whether the amount or quality of carbohydrate in diet is associated with ovulatory infertility. In total, 18,555 married, premenopausal women without a history of infertility were followed as they attempted a pregnancy or became pregnant during an 8-year period. Diet was assessed two times during follow-up using a validated food-frequency questionnaire and prospectively related to the incidence of infertility due ovulatory disorder. During follow-up, 438 women reported ovulatory infertility. Total carbohydrate intake and dietary glycemic load were positively related to ovulatory infertility in analyses adjusted for age, body mass index, smoking, parity, physical activity, recency of contraception, total energy intake, protein intake and other dietary variables. The multivariable-adjusted risk ratio (RR) (95% confidence interval (CI)) of ovulatory infertility comparing the highest-to-lowest quintile of total carbohydrate intake was 1.91 (1.27-3.02). The corresponding RR (95% CI) for dietary glycemic load was 1.92 (1.26-2.92). Dietary glycemic index was positively related to ovulatory infertility only among nulliparous women. Intakes of fiber from different sources were unrelated to ovulatory infertility risk. The amount and quality of carbohydrate in diet may be important determinants of ovulation and fertility in healthy women.


Chronic Pancreatitis-Induced Thrombosis of Celiac and Superior Mesenteric Artery.
Every year, nearly 60,000 hospitalizations occur in the United States due to chronic pancreatitis (CP). CP can cause severe chronic abdominal pain, pancreatic insufficiency, and increased risk of pancreatic cancer. While venous thrombotic complications are common, arterial thrombotic events are rarely reported in CP. This report describes a case of a 43-year-old female who presented with severe worsening abdominal pain due to CP. Diagnostic imaging disclosed thrombosis of superior mesenteric artery (SMA) and celiac artery (CA) with acute bowel wall changes reflecting ischemic changes, resulting in acute-on-chronic mesenteric ischemia. Endovascular stent placement relieved the ischemia with the resolution of pain. Arterial thrombosis should be considered as a diagnostic possibility when patients with CP present with a significant change in symptoms. Importantly, the case demonstrates that endovascular treatment with stent placement can relieve ischemia and resolve symptoms in patients with CP.


Pathogenesis of hepatocellular damage in chronic hepatitis C virus infection.
Multiple factors may influence the host-virus interaction in patients infected with hepatitis C virus (HCV), and these may result in diverse disease presentations. In immune competent hosts, there is little evidence that direct cytopathicity plays a significant role in liver cell injury. However, when host conditions are altered to allow for unusually high levels of viral replication and viral protein expression (i.e., immunosuppression), HCV may induce direct hepatocellular damage. In most patients infected with HCV, a wide array of humoral and cell-mediated immune responses are triggered in response to HCV polypeptides; however, despite this host immune response, HCV infections usually persist. Furthermore, the host immune response, in its attempt to clear the virus from the liver, contributes to the hepatocellular damage (chronic hepatitis) seen in the majority of chronically infected patients.


Molecular dynamics study of tropical calcific pancreatitis (TCP) associated calcium-sensing receptor single nucleotide variation.
Tropical Calcific Pancreatitis (TCP) is a chronic non-alcoholic pancreatitis characterised by extensive calcification. The disease usually appears at a younger age and is more common in tropical regions. This disease's progression can lead to pancreatic diabetes, which can subsequently lead to pancreatic cancer. The CASR gene encodes a calcium-sensing receptor (CaSR), which is a GPCR protein of class C. It is expressed in the islets of Langerhans, the parathyroid gland, and other tissues. It primarily detects small gradients in circulating calcium concentrations and couples this information to intracellular signalling, which helps to regulate PTH (parathyroid hormone) secretion and mineral ion homeostasis. From co-leading insulin release, CaSR modulates ductal HCO3- secretion, Ca2+ concentration, cell-cell communication, β-cell proliferation, and intracellular Ca2+ release. In pancreatic cancer, the CaSR limits cell proliferation. TCP-related four novel missense mutations P163R, I427S, D433H and V477A, found in CaSR extracellular domain (ECD) protein, which were reported in the mutTCPdb Database (https://lms.snu.edu.in/mutTCPDB/index.php). P163R mutation occurs in ligand-binding domain 1 (LBD-1) of the CaSR ECD. To investigate the influence of these variations on protein function and structural activity multiple in-silico prediction techniques such as SIFT, PolyPhen, CADD scores, and other methods have been utilized. A 500 ns molecular dynamic simulation was performed on the CaSR ECD crystal structure and the corresponding mutated models. Furthermore, Principal Component Analysis (PCA) and Essential Dynamics analysis were used to forecast collective motions, thermodynamic stabilities, and the critical subspace crucial to CaSR functions. The results of molecular dynamic simulations showed that the mutations P163R, I427S, D433H, and V477A caused conformational changes and decreased the stability of protein structures. This study also demonstrates the significance of TCP associated mutations. As a result of our findings, we hypothesised that the investigated mutations may have an effect on the protein's structure and ability to interact with other molecules, which may be related to the protein's functional impairment.


Piglet colibacillosis diagnosis based on multiplex polymerase chain reaction and immunohistochemistry of paraffin-embedded tissues.
Enterotoxigenic Escherichia coli (ETEC) causes diarrhea in pigs, referred to as colibacillosis. The aim of this study was to optimize multiplex polymerase chain reaction (PCR) and immunohistochemistry (IHC) analyses of paraffin-embedded material to detect pathogenic E. coli strains causing colibacillosis in pigs. Multiplex PCR was optimized for fimbriae (F18, F4, F6, F5, and F41) and toxins (types A and B heat-stable toxins [STaP and STb], heat-labile toxin [LT], and type 2 Shiga toxin [STx2e]), and IHC was optimized for an anti-E. coli polyclonal antibody. Samples (132) from pigs received between 2006 and 2014 with clinical and histopathological diagnoses of colibacillosis were analyzed. E. coli was detected by IHC in 78.7%, and at least one virulence factor gene was detected in 71.2%. Pathogenic strains of ETEC with at least one fimbria and one toxin were detected in 40% of the samples in multiplex PCR. The most frequent virulence types were F18-STaP (7.5%), F18-STaP-STb (5.7%), and F4-STaP (3.8%). A statistically significant association was noted between virulence factors F4, F18, STaP, and STb and positive immunostaining results. Colibacillosis diagnosis through multiplex PCR and IHC of paraffin-embedded tissues is a practical approach, as samples can be fixed and stored for long periods before analysis.


Motor fluctuations in Parkinson's disease: pathophysiology and treatment.
At the initial stages of Parkinson's disease (PD), levodopa (LD) is able to reduce most motor symptoms and to significantly improve the patient's quality of life. However, in the vast majority of patients with prolonged LD usage, some decline in efficacy occurs and motor complications eventually begin to appear. These complications consist not only of daily fluctuations in the voluntary motor performance often accompanied by involuntary movements, but also of fluctuations in cognitive, autonomic, and sensory functions. Several recent studies on LD complications in PD have led to a better understanding of their pathophysiology and of the possible therapeutic interventions, and a summary of these findings is presented in this review. Different observations now suggest that postsynaptic pharmacodynamic factors play a major role in determining fluctuations in PD. Two explanations are given: chronic intermittent dopaminergic therapy may lead to postsynaptic receptor downregulation in PD; or, receptor changes in the striatum may occur independently of treatment as a result of structural adaptation of the postsynaptic dopaminergic system to the progressive decline of the nigrostriatal pathway. The hypothesis of reversible postsynaptic changes as the main mechanism underlying a fluctuating response to LD lends itself to a possible pharmacological manipulation of the dopaminergic response to reverse, or even avoid, motor fluctuations (initial monotherapy with dopamine agonists and early combination LD/dopamine agonists). The role of peripheral pharmacokinetics factors is also critical and the use of controlled release LD formulations, of monoamine oxidase (MAO)-B and of catechol-O-methyltransferase (COMT) inhibitors may all, to a different degree, improve such phenomena. In the last decade, there has been a resurgence in surgical therapies in advanced PD, due to higher levels of accuracy and safety provided by the new surgical devices, and to a more precise localization of the target areas allowed by the neurophysiological mapping techniques. The surgical procedures currently used in advanced PD are stereotactic brain lesions (internal globus pallidus and subthalamic nucleus), chronic brain stimulation (of the same nuclei) and striatal grafting of dopamine-producing cells. All these procedures have already shown their efficacy in the management of severe fluctuations in PD, but their indications, and relative advantages and disadvantages, are still the subject of considerable debate and controversy.


[Ventricular septal defect and valvular aortic insufficiency. Our experience with nineteen patients (author's transl)].
Nineteen patients with ventricular septal defect (V.S.D) and valvular aortic insufficiency (A.I.), who underwent surgical repair, were reported. In the majority of patients the V.S.D. was localized in the supracristal region and the most frequent aortic valve abnormality was a prolapsing right cusp. Closure of the V.S.D. was effected with a patch in 15 patients and by direct suture in 4. Surgical management of A.I. consisted of: a) replacement of the aortic valve in 12 patients; b) no procedure on the aortic valve in 6 patient; c) plastic repair of the aortic valve in 1 patient. Only one patient died. Conservative management of the A.I. is advocated, but this is possible only if early repair is attempted. In adults, replacement with a prosthesis is indicated for severe A.I.


Absolute rates of protein synthesis during meiotic maturation of mammalian oocytes in vitro.
Measurements of the rates of incorporation of [35S]methionine into protein and the specific activities of endogenous free methionine pools have been used to calculate the absolute rates of protein synthesis in mouse oocytes during spontaneous meiotic maturation in vitro. Fluorodinitro[3H]benzene was used to determine the specific activity of the oocyte's free methionine pool. It was found that the absolute rate of protein synthesis decreased from 43 to 31 pg/hr per oocyte during meiotic progression from dictyate to metaphase II (meiotic maturation), while the size of the intracellular free methionine pool decreased from 61 to 35 fmol per oocyte during the same period. Comparable measurements made on ovulated mouse oocytes that had undergone meiotic maturation in vivo strongly suggest that the decrease in the absolute rate of protein synthesis observed during meiotic maturation in vitro is physiologically significant. An alternative method that depends upon differential expansion of the oocyte's endogenous methionine pool was also used to determine absolute rates of protein synthesis. The results of these experiments are in excellent agreement with those obtained by using fluorodinitro[3H]benzene, indicating that the oocyte's free methionine pool is not compartmentalized.


Imaging and therapeutic targeting of the tumor immune microenvironment with biologics.
The important role of tumor microenvironmental elements in determining tumor progression and metastasis has been firmly established. In particular, the presence and activity profile of tumor-infiltrating immune cells may be associated with the outcome of the disease and may predict responsiveness to (immuno)therapy. Indeed, while some immune cell types, such as macrophages, support cancer cell outgrowth and mediate therapy resistance, the presence of activated CD8+ T cells is usually indicative of a better prognosis. It is therefore of the utmost interest to obtain a full picture of the immune infiltrate in tumors, either as a prognostic test, as a way to stratify patients to maximize therapeutic success, or as therapy follow-up. Hence, the non-invasive imaging of these cells is highly warranted, with biologics being prime candidates to achieve this goal.


Outcomes of 122 diverse adult and pediatric cord blood transplant recipients from a large cord blood bank.
Umbilical cord blood is a useful stem cell source for some patients. The American Red Cross Cord Blood Program was established as a national network of cord blood banks. Nine thousand cord blood units were cryopreserved for transplant use. This report summarizes the experience with the first 125 cord blood units that have been distributed for transplant for 122 patients at 36 different transplant centers worldwide. Patients were treated with a variety of conditioning regimens. Most patients had acute myelogeneous leukemia (21%), genetic disorders (22%), or acute lymphoblastic leukemia (18%). The median age of the patients was 11 years with a range of 2 months to 63 years. The patients ranged in size from 3 to 120 kg (median, 39 kg). The median number of days to neutrophil engraftment was 22, and the median number of days to platelet engraftment was 63. Thirty percent of patients experienced Grades III to IV acute graft-versus-host disease (GVHD). Survival at 1 year after transplant was 35 percent, with recurrent disease the major cause of death. In multivariate analysis, only age less than 18 years was a significant predictor for improved survival. Forty-two percent of patients were non-Caucasian. Engraftment, GVHD, survival, and disease-free survival were similar among Caucasian and non-Caucasian patients. Umbilical cord blood serves as a satisfactory stem cell source for a diverse group of pediatric and adult patients.


Arthroscopic Excision of Osteoid Osteoma of the Talus.
Osteoid osteoma is a benign tumor that can cause significant pain and disability. Excision of the tumor can be accomplished with open surgery or, as advocated in recent years, with computed tomography (CT)-guided radiofrequency ablation. In this article, a unique arthroscopic approach to excise an osteoid osteoma of the talus is presented. This was possible by relying on a clear intra-articular prominent osteophyte, which was used as a landmark to indicate tumor location in accordance with preoperative CT views. This technique enabled excision of the tumor with concomitant arthroscopic decompression of the osteophyte, which contributed to symptoms of anterior ankle impingement.


Customizable Natural Language Processing Biomarker Extraction Tool.
Natural language processing (NLP) in pathology reports to extract biomarker information is an ongoing area of research. MetaMap is a natural language processing tool developed and funded by the National Library of Medicine to map biomedical text to the Unified Medical Language System Metathesaurus by applying specific tags to clinically relevant terms. Although results are useful without additional postprocessing, these tags lack important contextual information. Our novel method takes terminology-driven semantic tags and incorporates those into a semantic frame that is task-specific to add necessary context to MetaMap. We use important contextual information to capture biomarker results to support Community Health System's use of Precision Medicine treatments for patients with cancer. For each biomarker, the name, type, numeric quantifiers, non-numeric qualifiers, and the time frame are extracted. These fields then associate biomarkers with their context in the pathology report such as test type, probe intensity, copy-number changes, and even failed results. A selection of 6,713 relevant reports contained the following standard-of-care biomarkers for metastatic breast cancer: breast cancer gene 1 and 2, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and programmed death-ligand 1. The method was tested on pathology reports from the internal pathology laboratory at Henry Ford Health System. A certified tumor registrar reviewed 400 tests, which showed > 95% accuracy for all extracted biomarker types. Using this new method, it is possible to extract high-quality, contextual biomarker information, and this represents a significant advance in biomarker extraction.


Reduced CTL motility and activity in avascular tumor areas.
Patchy infiltration of tumors by cytotoxic T cells (CTLs) predicts poorer prognosis for cancer patients. The factors limiting intratumoral CTL dissemination, though, are poorly understood. To study CTL dissemination in tumors, we histologically examined human melanoma samples and used mice to image B16-OVA tumors infiltrated by OT-I CTLs using intravital two-photon microscopy. In patients, most CTLs concentrated around peripheral blood vessels, especially in poorly infiltrated tumors. In mice, OT-I CTLs had to cluster around tumor cells to efficiently kill them in a contact-and perforin-dependent manner and cytotoxicity was strictly antigen-specific. OT-I CTLs as well as non-specific CTLs concentrated around peripheral vessels, and cleared the tumor cells around them. This was also the case when CTLs were injected directly into the tumors. CTLs crawled rapidly only in areas within 50 µm of flowing blood vessels and transient occlusion of vessels immediately, though reversibly, stopped their migration. In vitro, oxygen depletion and blockade of oxidative phosphorylation also reduced CTL motility. Taken together, these results suggest that hypoxia limits CTL migration away from blood vessels, providing immune-privileged niches for tumor cells to survive. Normalizing intratumoral vasculature may thus synergize with tumor immunotherapy.


Optimal designs for a multiresponse Emax model and efficient parameter estimation.
The aim of dose finding studies is sometimes to estimate parameters in a fitted model. The precision of the parameter estimates should be as high as possible. This can be obtained by increasing the number of subjects in the study, N, choosing a good and efficient estimation approach, and by designing the dose finding study in an optimal way. Increasing the number of subjects is not always feasible because of increasing cost, time limitations, etc. In this paper, we assume fixed N and consider estimation approaches and study designs for multiresponse dose finding studies. We work with diabetes dose-response data and compare a system estimation approach that fits a multiresponse Emax model to the data to equation-by-equation estimation that fits uniresponse Emax models to the data. We then derive some optimal designs for estimating the parameters in the multi- and uniresponse Emax model and study the efficiency of these designs.


Reading and erasing of histone crotonyllysine mimics by the AF9 YEATS domain and SIRT2 deacylase.
Lysine acylations on histones and their recognition by chromatin-binding reader domains and removal by histone deacylases function as an important mechanism for eukaryotic gene regulation. Histone lysine crotonylation (Kcr) is an epigenetic mark associated with active transcription, and its installation and removal are dynamically regulated by cellular epigenetic enzymes. Here, we report binding studies and enzyme assays with histone H3K9 peptides bearing simplest Kcr analogs with varying hydrocarbon chain length, bulkiness, rigidity and polarity. We demonstrate that the AF9 YEATS domain displays selectivity for binding of different acylation modifications on histone H3K9 peptides and exhibits preference for bulkier cinnamoylated lysine over crotonylated lysine and its mimics. SIRT2 shows deacylase activity against most of acylated H3K9 peptides bearing different crotonyllysine mimics, however, it displays a poor ability for the removal of cinnamoyl and trifluorocrotonyl groups. These results demonstrate different substrate selectivities of epigenetic proteins acting on crotonyllysine and pave the way for rational design and development of AF9 YEATS and SIRT2 inhibitors for treatment of human diseases, including cancer.


Body sway and divided attention performance under the influence of alcohol: dose-response differences between males and females.
This study assessed women and men on a divided attention task, body sway, and subjective (self-report) estimates of impairment across different doses of alcohol. Twelve females and 12 males (mean age of 20.4 years) were given placebo, low, and high doses of alcohol in random order across sessions. Each subject was tested 3 times during each session. The study controlled for recent drinking history by restricting participation to light drinkers who were matched on age and education. Alcohol doses were adjusted for body fat and equivalent blood alcohol concentrations (BACs) were attained in the two gender groups. The results indicated that women and men did not differ in their extent of cognitive impairment at placebo and low alcohol doses. However, women showed significantly more cognitive impairment than their male counterparts at the high alcohol doses, even with equivalent BACs. The sway measure was influenced only by BAC and not by the gender of the subject. Sway observations were less sensitive and more variable than estimates of cognitive impairment. The subjective impairment data indicated that female subjects were less sensitive than males to the effects of alcohol at both the low and high doses. Implications for future research on cognitive impairment are discussed.


Outcomes of Information Seeking and Avoidance Behaviors: Insights from a German Longitudinal Study.
Examining information behaviors is often justified by their consequences but theoretical models of information behaviors have focused on antecedents of seeking and avoidance rather than their outcomes. Therefore, the current study aims to explore the affective, cognitive, and behavioral consequences of information-seeking and avoidance behaviors related to the COVID-19 pandemic. Based on a secondary analysis of a four-wave online survey of a sample of German residents (n = 492), we conducted hybrid models allowing us to differentiate between within-person effects of information behaviors on the outcomes and between-person correlations between information behaviors and outcomes. The findings revealed only single and small effects of information behaviors. Cognitive consequences such as risk perceptions were influenced by information seeking, whereas information seeking and avoidance affected individuals' subjective but not their objective level of knowledge. Neither information seeking nor avoidance impacted affective responses or a variety of behavioral consequences. These results contrast with assumptions that information seeking is per se a desirable health outcome, whereas information avoidance might be a barrier to health prevention and pandemic containment. At least in times of a health crisis, the findings suggest that information behavior might not be the central determinant of various affective, cognitive, and behavioral outcomes.


Influence of iron on microcin 25 production.
The effect of the iron content of the medium on the yield of the peptide antibiotic microcin 25 was examined; synthesis was optimal in minimal media and was reduced by adding iron. Escherichia coli AY25, the wild-type producer of the antibiotic, showed a 95% decrease in microcin yield when grown in minimal medium containing 10 microM iron (high iron) as compared to 0.2 microM (low iron). Addition of chelators to Luria broth elicited microcin production, and there was a complete reversal of the effect of the chelators by adding iron. Studies with Escherichia coli mutants deficient in iron-regulated proteins (fur) suggested that factors other than Fur could mediate iron regulation of microcin synthesis.


Pursuing a peaceful death.
To gain a better way of thinking about medical technology and our human mortality, we should begin backward. Death should be seen as the necessary and inevitable end point of medical care.... We as a society remain uncertain about the status of patients who manage to combine, in a bewildering way, elements of both life and death.


t(1;3)(p36;p21) is a recurring therapy-related translocation.
Chromosome bands 1p36 and 3p21 are known to be recurring breakpoints in therapy-related (t-) leukemia. We identified a recurring translocation, t(1;3)(p36;p21), in eight patients with various hematologic malignancies: three patients with ALL, one with chronic myelogenous leukemia (CML) in accelerated phase (AP), two with MDS, and two with AML(M3). Five of the eight patients had a history of chemotherapy, including alkylating agents in three, before the translocation was detected. In two of these five patients, the t(1;3)(p36;p21) emerged only at relapse or in the accelerated phase of CML. The karyotypes of the patients were complex, including -7 and structural abnormalities of 5q, 6q, 7q, 9p, and 11q23. Survival time varied among patients (25 days to more than 16 years). Using FISH with 13 1p35-36 cosmid probes (tel-FB12-CA5-G7-FD2-CB1-ED8-FD9-G32-AE3-G50-AD8-GG4-G43-cen), we delineated the 1p36 breakpoint in two patients with MDS and ALL as lying between FB12 and FD2 (between BAC47P3 and PAC963K15), with a small deletion near the breakpoint in both cases. In the patient with MDS, there was also a deletion at 3p21.3, as detected with the cosmid probe cosNRL9. The results of the present study suggest that t(1;3)(p36;p21) in hematologic diseases is associated with prior exposure to mutagens, including alkylating agents.


Biological Treatments for Tendon and Ligament Abnormalities: A Critical Analysis Review.
The poor intrinsic healing potential of tendon and ligamentous tissue has driven the search for biological agents that can improve healing, most notably platelet-rich plasma (PRP) and autologous stem cells. Current evidence best supports the use of PRP as treatment for chronic, degenerative tendinopathies such as lateral epicondylitis of the elbow or patellar tendinopathy. It does not support the use of PRP to promote tendon or ligament-to-bone healing in rotator cuff repair or anterior cruciate ligament (ACL) reconstruction. Clinical evidence regarding the use of autologous stem cells as treatment for tendon and ligament abnormalities is currently limited. However, the initial results appear to be promising, particularly following rotator cuff repair. A major limitation in the evaluation of current data is the lack of standardization in the preparation and composition of PRP, which are often not reported. Future investigators should make an effort to report the method of preparation and final composition of PRP used. Autologous stem cells were most often harvested from bone marrow aspirate but were occasionally derived from dermal tenocyte cells. Recent studies have explored new sources for stem cells, including adipose tissue, peripheral blood, and human amniotic tissue. We expect that clinical data evaluating these treatments will soon emerge.


Down-regulation of focal adhesion kinase, pp125FAK, in endothelial cell retraction during tumor cell invasion.
Although endothelial cell retraction is required before tumor cell invasion, its molecular mechanism still remains obscure. We previously demonstrated that conditioned medium (CM) derived from a human pancreatic cancer cell line, PSN-1, induced endothelial cell retraction and facilitated tumor cell invasion. To investigate the molecular change of events in the transduction of extracellular signals during endothelial cell retraction, we examined the effect of the CM derived from PSN-1 cells on the tyrosine phosphorylation in endothelial cells. Immunoblot analyses revealed that the PSN-1 CM decreased tyrosine phosphorylation of a 120-130 kD protein, and induced the concomitant down-regulation of focal adhesion kinase, pp125FAK, during endothelial cell retraction in time- and dose-dependent fashions. These changes preceded endothelial cell retraction and were reversible after removal of the CM. Further quantitative densitometric analyses demonstrated that the extent of decrease in tyrosine phosphorylated 120-130 kD protein during the endothelial cell retraction was likely to be proportional to that of the down-regulation of pp125FAK. A tyrosine phosphorylated 120-130 kD protein immunoprecipitated by anti-phosphotyrosine antibody immunoreacted with anti-pp125FAK antibody. These results suggested that decreased amount of a tyrosine phosphorylated 120-130 kD protein probably due to the down-regulation of pp125FAK might be associated with the signal transduction pathway in the endothelial cells during their retraction. Furthermore, these findings were also observed in the CM from another four human cancer cell lines, suggesting the down-regulation of pp125FAK in endothelial cells during tumor cell invasion.


Coherent transfer of nuclear spin polarization in field-cycling NMR experiments.
Coherent polarization transfer effects in a coupled spin network have been studied over a wide field range. The transfer mechanism is based on exciting zero-quantum coherences between the nuclear spin states by means of non-adiabatic field jump from high to low magnetic field. Subsequent evolution of these coherences enables conversion of spin order in the system, which is monitored after field jump back to high field. Such processes are most efficient when the spin system passes through an avoided level crossing during the field variation. The polarization transfer effects have been demonstrated for N-acetyl histidine, which has five scalar coupled protons; the initial spin order has been prepared by applying RF-pulses at high magnetic field. The observed oscillatory transfer kinetics is taken as a clear indication of a coherent mechanism; level crossing effects have also been demonstrated. The experimental data are in very good agreement with the theoretical model of coherent polarization transfer. The method suggested is also valid for other types of initial polarization in the spin system, most notably, for spin hyperpolarization.


From ideas to studies: how to get ideas and sharpen them into research questions.
Where do new research questions come from? This is at best only partially taught in courses or textbooks about clinical or epidemiological research. Methods are taught under the assumption that a researcher already knows the research question and knows which methods will fit that question. Similarly, the real complexity of the thought processes that lead to a scientific undertaking is almost never described in published papers. In this paper, we first discuss how to get an idea that is worth researching. We describe sources of new ideas and how to foster a creative attitude by "cultivating your thoughts". Only a few of these ideas will make it into a study. Next, we describe how to sharpen and focus a research question so that a study becomes feasible and a valid test of the underlying idea. To do this, the idea needs to be "pruned". Pruning a research question means cutting away anything that is unnecessary, so that only the essence remains. This includes determining both the latent and the stated objectives, specific pruning questions, and the use of specific schemes to structure reasoning. After this, the following steps include preparation of a brief protocol, conduct of a pilot study, and writing a draft of the paper including draft tables. Then you are ready to carry out your research.


Dendritic Cells in HIV-1 and HCV Infection: Can They Help Win the Battle?
Persistent infections with human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) are a major cause of morbidity and mortality worldwide. As sentinels of our immune system, dendritic cells (DCs) play a central role in initiating and regulating a potent antiviral immune response. Recent advances in our understanding of the role of DCs during HIV-1 and HCV infection have provided crucial insights into the mechanisms employed by these viruses to impair DC functions in order to evade an effective immune response against them. Modulation of the immunological synapse between DC and T-cell, as well as dysregulation of the crosstalk between DCs and natural killer (NK) cells, are emerging as two crucial mechanisms. This review focuses on understanding the interaction of HIV-1 and HCV with DCs not only to understand the immunopathogenesis of chronic HIV-1 and HCV infection, but also to explore the possibilities of DC-based immunotherapeutic approaches against them. Host genetic makeup is known to play major roles in infection outcome and rate of disease progression, as well as response to anti-viral therapy in both HIV-1 and HCV-infected individuals. Therefore, we highlight the genetic variations that can potentially affect DC functions, especially in the setting of chronic viral infection. Altogether, we address if DCs' potential as critical effectors of antiviral immune response could indeed be utilized to combat chronic infection with HIV-1 and HCV.


The effectiveness of an amine fluoride/stannous fluoride dentifrice on the gingival health of teenagers: results after six months.
The objectives of the present study included examining the effect of non-supervised tooth brushing with an amine fluoride/stannous fluoride (AmF/SnF2) dentifrice on gingival health of teenagers in a field trial over six months. Jerusalem high-school adolescents (246) participated in a double-blind study with a NaF dentifrice serving as control. No oral hygiene instruction or supervision was given. Examinations took place at baseline, three weeks, three months and six months. In all examinations, no differences were revealed for plaque levels. Other results indicated a consistent advantage for the AmF/SnF2 group. Gingival Index (GI) scores were significantly lower in the test group at the three month examination (GI = 0.85, compared to GI = 0.89; p = 0.036) and at the six month examination (GI = 0.72, compared to 0.78; p = 0.042) than among controls. Mean bleeding on probing scores were lower in the AmF/SnF2 than in the control group at the six month examination (0.53, compared to 0.63; p = 0.041). No side effects, including staining, were reported, nor found, among the AmF/SnF2 group. In addition to the well established caries preventive role of fluoride dentifrice, these data indicate an additional and important public health role of a AmF/SnF2 dentifrice, in preventing gingivitis.


The effect of 5 alpha-dihydrotestosterone and 5 beta-dihydrotestosterone on erythropoiesis of the newt, Triturus cristatus carnifex (Laur.).
The erythropoietic effects of 5 alpha-dihydrotestosterone (5 alpha-DHT) and 5 beta-dihydrotestosterone (5 beta-DHT) were compared in the newt, Triturus cristatus carnifex (Laur.). In normal animals, 5 beta-DHT was more active than 5 alpha-DHT in increasing the number of circulating erythrocytes. In animals rendered completely anemic, only 5 beta-DHT was effective. The biochemical parameters of delta-aminolevulinic acid synthase and delta-aminolevulinic acid dehydratase of new basophilic erythroblasts, and incorporation of labeled glycine into heme and globin of new polychromatic erythroblasts were enhanced by 5 beta-DHT. The results are discussed with reference to a direct erythropoietin-independent action of 5 beta-DHT on erythroid stem cells.


Immunoglobulins in periodontal tissues. III. Concentrations of immunoglobulins in dilantin-induced and idiopathic gingival hyperplastic tissues.
Immunoglobulin levels in both Dilantin-induced and idiopathic hyperplastic gingiva were determined and compared with the concentrations in normal gingival tissue. A statistically significant increase in IgG was found in Dilantin hyperplastic tissue, but no significant difference could be shown for idiopathic gingival hyperplasia. IgA levels did not differ significantly in the three types of tissue assayed. IgM was detected in 90% of the Dilantin hyperplastic gingival specimens assayed (mean GI = 1.2) and in 75% of the idiopathic hyperplastic tissue (mean GI = 0.7). This incidence of IgM detection was higher than that reported for normal and inflamed gingiva from periodontitis patients. The significance of these findings and possible correlation with the degree of tissue inflammation are discussed.


The Effects of Crocus sativus (Saffron) on ADHD: A Systematic Review.
Crocus sativus also known as saffron, is one of the most popular traditional plants. This study aims to evaluate the efficacy and safety of saffron extracts in ADHD. This study includes clinical trial studies that assessed the efficacy and/or safety of saffron in ADHD patients. Non-English papers, review articles, commentaries, letters, observational studies, thesis, animal studies, in-vitro studies, and conference abstracts were not included. The risk of bias in randomized studies was evaluated based on the Cochrane RoB.2, and risk of bias in pre-post intervention studies was assessed using the ROBINS-I tool. Four studies met our inclusion criteria with a total of 118 patients. The results manifested an efficient role of saffron as either an adjuvant therapy to MPH or a single therapy against ADHD, without significant safety issues. Saffron demonstrates promise in improving ADHD symptoms, with an acceptable safety profile. Future well-designed multicentral studies are suggested.


Orthodontic reconstruction in a victim of murder.
Accurate comparison of ante-mortem photographs and the skull of a deceased person is dependent upon suitable superimposition techniques and a post-mortem dentition which is comparable to the situation obtaining in the individual at the time of death. The skull featuring in this case presented with a missing upper lateral incisor, lost after death, and the occlusion was studied enabling a replacement tooth to be provided and positioned as in life. Although no dental records were available, good quality photographs of a putative identity were compared by electronic superimposition and the restored occlusal characteristics of the skull were shown to accurately match the photographs of one possible victim. This evidence resulted in positive identification by a Coroner. This case illustrates the importance of seeking specialist clinical advice in forensic dental cases.


Microplastics in wastewater treatment plants: Detection, occurrence and removal.
Microplastics have aroused increasing concern as they pose threats to aquatic species as well as human beings. They do not only contribute to accumulation of plastics in the environment, but due to absorption they can also contribute to spreading of micropollutants in the environment. Studies indicated that wastewater treatment plants (WWTPs) play an important role in releasing microplastics to the environment. Therefore, effective detection of the microplastics and understanding their occurrence and fate in WWTPs are of great importance towards microplastics control. In this review, the up-to-date status on the detection, occurrence and removal of microplastics in WWTPs are comprehensively reviewed. Specifically, the different techniques used for collecting microplastics from both wastewater and sewage sludge, and their pretreatment and characterization methods are reviewed and analyzed. The key aspects regarding microplastics occurrence in WWTPs, such as concentrations, total discharges, materials, shapes and sizes are summarized and compared. Microplastics removal in different treatment stages and their retention in sewage sludge are explored. The development of potential microplastics-targeted treatment technologies is also presented. Although previous researches in microplastics have undoubtedly improved our level of understanding, it is clear that much remains to be learned about microplastics in WWTPs, as many unanswered questions and thereby concerns still remain; some of these important future research areas are outlined. The key challenges appear to be to harmonize detection methods as well as microplastics mitigation from wastewater and sewage sludge.


Vaginal treatment of endometrial cancer: role in the elderly.
To compare abdominal hysterectomy, the most currently used for treating cancer of the endometrium, to the vaginal hysterectomy in term of survival, morbidity and failure rates. We retrospectively analyzed 68 cases divided into two sub-groups. A study group of 31 cases received vaginal surgery; a control group of 37 cases was treated with a laparotomy. Mean operative time, median hospital stay, intra- and post-operative complications, DFS and OS time as well as occurrence of local or distant recurrences have been evaluated and reported. Cases included patients with a higher rate of medical morbidities (p = 0.01) than controls. Mean age was 76.2 and 70.4 years in the vaginal (V) group and abdominal (A) group respectively. Mean operative time was longer for the group A. Group V patients had a lower mean post-operative hospital stay (p < 0.05). Differences in the two groups regarding intra- and post-operative complications, occurrence of local or distant recurrences and DFS time were not statistically significant. Disease specific survival time at 5 years scored 97% for group V, and 97% for group A. Results show how vaginal approach had a similar outcome in selected patients. Vaginal surgery could therefore be the proper choice in patients with early stages and lower surgical risk, in addition to elderly patients exposed to a higher surgical risk.


Two-minute walk test: Reference equations for healthy adults in China.
Although the six-minute walk test (6MWT) is widely used as a measure of exercise capacity, it may not be applicable in some settings and populations. This issue has led to increased use of the two-minute walk test (2MWT) to assess exercise capacity. The main objective of this study is to establish reference equations for the two-minute walk distance (2MWD) in healthy Chinese adults aged 18-85 years. A total of 973 volunteers took part in the study. We obtained verbal consent from all participants before the test, and the study design was approved by the ethics committees of Wenzhou People's Hospital. The participants performed two 2MWTs using a standardized protocol, and the longer distance was used for further analysis. Stepwise multiple regression analysis was performed using age, height and weight as independent variables and was used to establish the reference equations for the 2MWD in the male and female groups. The mean walking distance for all participants was 199.1±25.81 m. Age and height were identified as independent factors that influenced the 2MWD, and they explained 35% and 34% of the variance in distance for the male and female groups, respectively. This study resulted in determination of reference equations for predicting the 2MWD in healthy Chinese adults. These 2MWD standards will provide useful references for medical care in some settings and populations.


High stathmin 1 expression is associated with poor prognosis and chemoradiation resistance in esophageal squamous cell carcinoma.
Stathmin 1 (STMN1) is a major cytosolic phosphoprotein regulating microtubule dynamics, thereby playing an important role in cancer progression and resistance to microtubule-binding anticancer agents. We assessed the prognostic significance of STMN1 expression and STMN1-associated resistance to docetaxel and radiation in esophageal squamous cell carcinoma (ESCC) patients. STMN1 expression was evaluated by immunohistochemistry in 172 surgical specimens. The association of STMN1 expression with chemoradiation resistance using docetaxel was examined by comparing expression in 15 biopsy specimens obtained before neoadjuvant therapy to histological grades of post-therapy surgically resected tumors. We also evaluated the effects of STMN1 on sensitivity to docetaxel and radiation in ESCC cell lines. High STMN1 immunoexpression was significantly associated with tumor depth, lymph node metastasis, lymphatic invasion and venous invasion. Survival rates were significantly lower in ESCC patients with high STMN1 expression than in those with low STMN1 expression. Multivariable analysis showed that high STMN1 expression was an independent factor for poor survival. High STMN1 expression was also associated with poor response to neoadjuvant chemoradiotherapy using docetaxel. Knockdown of STMN1 expression enhanced ESCC cell line sensitivity to docetaxel and radiation. STMN1 appears critical for ESCC invasiveness and predicts an unfavorable prognosis in ESCC.


Prevalence and genotypic identification of Cryptosporidium spp., Giardia duodenalis and Enterocytozoon bieneusi in pre-weaned dairy calves in Guangdong, China.
Cryptosporidium spp., Giardia duodenalis and Enterocytozoon bieneusi are common enteric pathogens in humans and animals. Data on the transmission of these pathogens are scarce from Guangdong, China, which has a subtropical monsoon climate and is the epicenter for many emerging infectious diseases. This study was conducted to better understand the prevalence and identity of the three pathogens in pre-weaned dairy calves in Guangdong. The occurrence and genetic identity of three pathogens were analyzed by polymerase chain reaction. PCR-positive products were sequenced to determine the species and genotypes. A Chi-square test was used to compare the prevalence of pathogens among sampling dates, age groups, or clinical signs. The detection rates of Cryptosporidium spp., G. duodenalis and E. bieneusi were 24.0% (93/388), 74.2% (288/388) and 15.7% (61/388), respectively. Three Cryptosporidium species were detected, including C. bovis (n = 73), C. parvum (n = 12) and C. ryanae (n = 7); one animal had concurrence of C. bovis and C. parvum. C. parvum was the dominant species during the first two weeks of life, whereas C. bovis and C. ryanae were mostly seen at 3-9 weeks of age. Sequence analysis identified the C. parvum as subtype IIdA19G1. Assemblage E (n = 282), assemblage A (n = 1), and concurrence of A and E (n = 5) were identified among G. duodenalis-positive animals using multilocus genotyping (MLG). Altogether, 15, 10 and 17 subtypes of assemblage E were observed at the bg, gdh and tpi loci, respectively, forming 49 assemblage E MLGs. The highest detection rate of G. duodenalis was found in winter. Sequence analysis identified genotypes J (n = 57), D (n = 3) and one concurrence of J and D among E. bieneusi-positive animals. The detection rate of E. bieneusi was significantly higher in spring (38.0%; 41/108) than in summer (7.2%; 8/111) and winter (7.1%; 12/169). These results indicate a common occurrence of C. parvum subtype IIdA19G1, G. duodenalis assemblage E, and E. bieneusi genotype J in pre-weaned dairy calves in Guangdong. More studies are needed to understand the unique genetic characteristics and zoonotic potential of the three enteric pathogens in the province.


Research on defects inspection of solder balls based on eddy current pulsed thermography.
In order to solve tiny defect detection for solder balls in high-density flip-chip, this paper proposed feasibility study on the effect of detectability as well as classification based on eddy current pulsed thermography (ECPT). Specifically, numerical analysis of 3D finite element inductive heat model is generated to investigate disturbance on the temperature field for different kind of defects such as cracks, voids, etc. The temperature variation between defective and non-defective solder balls is monitored for defects identification and classification. Finally, experimental study is carried on the diameter 1mm tiny solder balls by using ECPT and verify the efficacy of the technique.


Future directions of environmental public health research: ATSDR's 2002-2010 agenda for six priority focus areas.
Additional research on human exposures to hazardous substances in community settings and resultant adverse health effects is needed to fill an extensive number of information gaps. For example, information is needed to answer specific public health questions about the toxic effects of specific chemicals, who has been exposed, what the health risks might be, and what interventions are effective. The Agency for Toxic Substances and Disease Registry (ATSDR) is the principal federal agency responsible for addressing issues of public health concerning the human health risks associated with hazardous waste sites and unplanned releases of hazardous substances into the environment. Research is a critical component in how effectively the agency can identify persons exposed, determine health risks, and intervene to reduce exposures and adverse health outcomes. ATSDR has recently developed an agenda for public health environmental research for 2002-2010, divided into the following six research focus areas: exposure assessment; chemical mixtures; susceptible populations; community and tribal involvement; evaluation and surveillance of health effects; and health promotion and intervention. This article discusses the agenda's development, the research issues within each of the six focus areas, and preliminary implementation plans.


[Progressive bulbopontine paralysis in children].
A case of pons-bulbar palsy in a 10 year-old girl is reported. The authors insist on the fact that motor cranial nerve nuclear dysfunction was isolated, without any pyramidal tract disorder. They also emphasize the slow course of the disease, which after one year of quick progression was stable for the next 5 years. Nineteen identical cases were found in the literature. From this nosographic group, one must exclude patients with associated lateral spinal tract dysfunction: these patients must be discussed with the juvenile or infantile amyotrophic lateral sclerosis group. The heterogeneity of the pons-bulbar paralysis group is also underlined: the course may be quickly fatal or, on the contrary, protracted for a long time; genetic transmission is also quite variable.


Whey protein intake after resistance exercise activates mTOR signaling in a dose-dependent manner in human skeletal muscle.
Protein ingestion after resistance exercise increases muscle protein synthesis (MPS) in a dose-dependent manner. However, the molecular mechanism(s) for the dose-dependency of MPS remains unclear. This study aimed to determine the dose response of mammalian target of rapamycin (mTOR) signaling in muscle with ingestion of protein after resistance exercise. Fifteen male subjects performed four sets of six unilateral isokinetic concentric knee extensions. Immediately after exercise, eight subjects consumed water only. The other seven subjects, in a randomized-order crossover design, took either a 10 [3.6 g essential amino acids (EAA)] or 20 g (7.1 g EAA) solution of whey protein. Muscle biopsies from the vastus lateralis muscle were taken 30 min before and 1 h after resistance exercise. Phosphorylation of Akt (Ser473), mTOR (Ser2448), 4E-BP1 (Thr37/46), and S6K1 (Thr389) was measured by western blotting. Concentric knee extension exercise alone did not increase phosphorylation of Akt and mTOR 1 h after exercise, but ingesting protein after exercise significantly increased the phosphorylation of Akt and mTOR in a dose-dependent manner (P < 0.05). 4E-BP1 phosphorylation significantly decreased after resistance exercise (P < 0.05), but subjects who took 10 or 20 g of protein after exercise showed increased 4E-BP1 from post-exercise dephosphorylation (P < 0.05). S6K1 phosphorylation significantly increased after resistance exercise (P < 0.05), and 20 g of protein further increased S6K1 phosphorylation compared with ingestion of 10 g (P < 0.05). These findings suggest that whey protein intake after resistance exercise activates mTOR signaling in a dose-dependent manner in untrained men.


Identification of CMS as a cytosolic adaptor of the human pTalpha chain involved in pre-TCR function.
The T-cell receptor beta (TCRbeta)/pre-TCRalpha (pTalpha) pre-TCR complex (pre-TCR) signals the expansion and differentiation of de-veloping thymocytes. Functional pro-perties of the pre-TCR rely on its unique pTalpha chain, which suggests the participation of specific intracellular adaptors. However, pTalpha-interacting molecules remain unknown. Here, we identified a polyproline-arginine sequence in the human pTalpha cytoplasmic tail that interacted in vitro with SH3 domains of the CIN85/CMS family of adaptors, and mediated the recruitment of multiprotein complexes involving all (CMS, CIN85, and CD2BP3) members. Supporting the physiologic relevance of this interaction, we found that 1 such adaptor, CMS, interacted in vivo with human pTalpha, and its expression was selectively up-regulated during human thymopoiesis in pre-TCR-activated thymocytes. Upon activation, pre-TCR clustering was induced, and CMS and polymerized actin were simultaneously recruited to the pre-TCR activation site. CMS also associated via its C-terminal region to the actin cytoskeleton in the endocytic compartment, where it colocalized with internalized pTalpha in traffic to lysosomal degradation. Notably, deletion of the pTalpha CIN85/CMS-binding motif impaired pre-TCR-mediated Ca(2+) mobilization and NFAT transcriptional activity, and precluded activation induced by overexpression of a CMS-SH3 N-terminal mutant. These results provide the first molecular evidence for a pTalpha intracellular adaptor involved in pre-TCR function.